title: Menopausal hormone therapy and health outcomes during the intervention and extended poststopping phases of the Women's Health Initiative randomized trials.
abstract: OBJECTIVE
  Menopausal hormone therapy continues in clinical use but questions remain regarding its risks and benefits for chronic disease prevention.
  
  
  OBJECTIVE
  To report a comprehensive, integrated overview of findings from the 2 Women's Health Initiative (WHI) hormone therapy trials with extended postintervention follow-up.
  
  
  METHODS
  A total of 27,347 postmenopausal women aged 50 to 79 years were enrolled at 40 US centers.
  
  
  METHODS
  Women with an intact uterus received conjugated equine estrogens (CEE; 0.625 mg/d) plus medroxyprogesterone acetate (MPA; 2.5 mg/d) (n = 8506) or placebo (n = 8102). Women with prior hysterectomy received CEE alone (0.625 mg/d) (n = 5310) or placebo (n = 5429). The intervention lasted a median of 5.6 years in CEE plus MPA trial and 7.2 years in CEE alone trial with 13 years of cumulative follow-up until September 30, 2010.
  
  
  METHODS
  Primary efficacy and safety outcomes were coronary heart disease (CHD) and invasive breast cancer, respectively. A global index also included stroke, pulmonary embolism, colorectal cancer, endometrial cancer, hip fracture, and death.
  
  
  RESULTS
  During the CEE plus MPA intervention phase, the numbers of CHD cases were 196 for CEE plus MPA vs 159 for placebo (hazard ratio [HR], 1.18; 95% CI, 0.95-1.45) and 206 vs 155, respectively, for invasive breast cancer (HR, 1.24; 95% CI, 1.01-1.53). Other risks included increased stroke, pulmonary embolism, dementia (in women aged ≥65 years), gallbladder disease, and urinary incontinence; benefits included decreased hip fractures, diabetes, and vasomotor symptoms. Most risks and benefits dissipated postintervention, although some elevation in breast cancer risk persisted during cumulative follow-up (434 cases for CEE plus MPA vs 323 for placebo; HR, 1.28 [95% CI, 1.11-1.48]). The risks and benefits were more balanced during the CEE alone intervention with 204 CHD cases for CEE alone vs 222 cases for placebo (HR, 0.94; 95% CI, 0.78-1.14) and 104 vs 135, respectively, for invasive breast cancer (HR, 0.79; 95% CI, 0.61-1.02); cumulatively, there were 168 vs 216, respectively, cases of breast cancer diagnosed (HR, 0.79; 95% CI, 0.65-0.97). Results for other outcomes were similar to CEE plus MPA. Neither regimen affected all-cause mortality. For CEE alone, younger women (aged 50-59 years) had more favorable results for all-cause mortality, myocardial infarction, and the global index (nominal P < .05 for trend by age). Absolute risks of adverse events (measured by the global index) per 10,000 women annually taking CEE plus MPA ranged from 12 excess cases for ages of 50-59 years to 38 for ages of 70-79 years; for women taking CEE alone, from 19 fewer cases for ages of 50-59 years to 51 excess cases for ages of 70-79 years. Quality-of-life outcomes had mixed results in both trials.
  
  
  CONCLUSIONS
  Menopausal hormone therapy has a complex pattern of risks and benefits. Findings from the intervention and extended postintervention follow-up of the 2 WHI hormone therapy trials do not support use of this therapy for chronic disease prevention, although it is appropriate for symptom management in some women.
  
  
  BACKGROUND
  clinicaltrials.gov Identifier: NCT00000611.
authors.affiliation: Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02215, USA. jmanson@rics.bwh.harvard.edu
authors.forename: JoAnn E
authors.initials: JE
authors.lastname: Manson
authors.forename: Rowan T
authors.initials: RT
authors.lastname: Chlebowski
authors.forename: Marcia L
authors.initials: ML
authors.lastname: Stefanick
authors.forename: Aaron K
authors.initials: AK
authors.lastname: Aragaki
authors.forename: Jacques E
authors.initials: JE
authors.lastname: Rossouw
authors.forename: Ross L
authors.initials: RL
authors.lastname: Prentice
authors.forename: Garnet
authors.initials: G
authors.lastname: Anderson
authors.forename: Barbara V
authors.initials: BV
authors.lastname: Howard
authors.forename: Cynthia A
authors.initials: CA
authors.lastname: Thomson
authors.forename: Andrea Z
authors.initials: AZ
authors.lastname: LaCroix
authors.forename: Jean
authors.initials: J
authors.lastname: Wactawski-Wende
authors.forename: Rebecca D
authors.initials: RD
authors.lastname: Jackson
authors.forename: Marian
authors.initials: M
authors.lastname: Limacher
authors.forename: Karen L
authors.initials: KL
authors.lastname: Margolis
authors.forename: Sylvia
authors.initials: S
authors.lastname: Wassertheil-Smoller
authors.forename: Shirley A
authors.initials: SA
authors.lastname: Beresford
authors.forename: Jane A
authors.initials: JA
authors.lastname: Cauley
authors.forename: Charles B
authors.initials: CB
authors.lastname: Eaton
authors.forename: Margery
authors.initials: M
authors.lastname: Gass
authors.forename: Judith
authors.initials: J
authors.lastname: Hsia
authors.forename: Karen C
authors.initials: KC
authors.lastname: Johnson
authors.forename: Charles
authors.initials: C
authors.lastname: Kooperberg
authors.forename: Lewis H
authors.initials: LH
authors.lastname: Kuller
authors.forename: Cora E
authors.initials: CE
authors.lastname: Lewis
authors.forename: Simin
authors.initials: S
authors.lastname: Liu
authors.forename: Lisa W
authors.initials: LW
authors.lastname: Martin
authors.forename: Judith K
authors.initials: JK
authors.lastname: Ockene
authors.forename: Mary Jo
authors.initials: MJ
authors.lastname: O'Sullivan
authors.forename: Lynda H
authors.initials: LH
authors.lastname: Powell
authors.forename: Michael S
authors.initials: MS
authors.lastname: Simon
authors.forename: Linda
authors.initials: L
authors.lastname: Van Horn
authors.forename: Mara Z
authors.initials: MZ
authors.lastname: Vitolins
authors.forename: Robert B
authors.initials: RB
authors.lastname: Wallace
mesh_terms: D000368:Aged; D001943:Breast Neoplasms / Q000453:epidemiology / Q000517:prevention & control*; D015179:Colorectal Neoplasms / Q000453:epidemiology; D003327:Coronary Disease / Q000453:epidemiology / Q000517:prevention & control*; D004359:Drug Therapy, Combination; D016889:Endometrial Neoplasms / Q000453:epidemiology; D004967:Estrogens / Q000008:administration & dosage* / Q000009:adverse effects; D004966:Estrogens, Conjugated (USP) / Q000008:administration & dosage* / Q000009:adverse effects; D005260:Female; D005500:Follow-Up Studies; D006620:Hip Fractures / Q000453:epidemiology; D020249:Hormone Replacement Therapy / Q000009:adverse effects*; D006801:Humans; D017258:Medroxyprogesterone Acetate / Q000008:administration & dosage* / Q000009:adverse effects; D008875:Middle Aged; D017698:Postmenopause; D011655:Pulmonary Embolism / Q000453:epidemiology; D011788:Quality of Life; D012306:Risk; D020521:Stroke / Q000453:epidemiology; D016896:Treatment Outcome; D014481:United States / Q000453:epidemiology
chemical_list: D004967:Estrogens; D004966:Estrogens, Conjugated (USP); D017258:Medroxyprogesterone Acetate